Hwang, Ara B. Ryu, Eun-A Artan, Murat Chang, Hsin-Wen Kabir, Mohammad Humayun Nam, Hyun-Jun Lee, Dongyeop Yang, Jae-Seong Kim, Sanguk Mair, William B. Lee, Cheolju Lee, Siu Sylvia Lee, Seung-Jae 2024-01-20T08:33:37Z 2024-01-20T08:33:37Z 2021-09-02 2014-10-21 0027-8424 https://pubs.kist.re.kr/handle/201004/126224 Mild inhibition of mitochondrial respiration extends the lifespan of many species. In Caenorhabditis elegans, reactive oxygen species (ROS) promote longevity by activating hypoxia-inducible factor 1 (HIF-1) in response to reduced mitochondrial respiration. However, the physiological role and mechanism of ROS-induced longevity are poorly understood. Here, we show that a modest increase in ROS increases the immunity and lifespan of C. elegans through feedback regulation by HIF-1 and AMP-activated protein kinase (AMPK). We found that activation of AMPK as well as HIF-1 mediates the longevity response to ROS. We further showed that AMPK reduces internal levels of ROS, whereas HIF-1 amplifies the levels of internal ROS under conditions that increase ROS. Moreover, mitochondrial ROS increase resistance to various pathogenic bacteria, suggesting a possible association between immunity and long lifespan. Thus, AMPK and HIF-1 may control immunity and longevity tightly by acting as feedback regulators of ROS. English NATL ACAD SCIENCES ACTIVATED PROTEIN-KINASE INCREASING OXIDATIVE STRESS LIFE-SPAN C. ELEGANS UNCOUPLING PROTEIN-2 ELECTRON-TRANSPORT HYPOXIA METABOLISM RESISTANCE GENES Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans Article 10.1073/pnas.1411199111 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.111, no.42, pp.E4458 - E4467 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111 42 E4458 E4467 scie scopus 000343302600011 2-s2.0-84908068704 Multidisciplinary Sciences Science & Technology - Other Topics Article ACTIVATED PROTEIN-KINASE INCREASING OXIDATIVE STRESS LIFE-SPAN C. ELEGANS UNCOUPLING PROTEIN-2 ELECTRON-TRANSPORT HYPOXIA METABOLISM RESISTANCE GENES aging mitochondria immunity reactive oxygen species C. elegans